Evidence exists of an association between diethylstilbestrol (DES) administration to humans and vaginal adenocarcinomas, but an association between steroidal estrogens and human malignances has not been established. In view of the wide use of estrogenic compounds in human medicine this remains an important unsolved problem. We have shown that chronic DES administration is associated with the development of a high frequency of invasive tumors arising from the uterine serosa in squirrel monkeys. We will use this unique primate model to test the hypothesis that carcinogenicity is a general property of physiologically active estrogens by administration of a variety of steroidal hormones. Determination of plasma levels of administered steroids by radioimmunoassay, and determination of hormone binding by in vivo radioactive uptake studies and in vitro receptor binding measurements before and during tumorigenesis and after hormone withdrawal will provide some important insights into steroid induced tumors which could suggest new principles for therapy. These experiments will also permit light and electron microscopic studies of the histogenesis and morphology of serosal lesions in the monkey for comparison with tumors arising from pelvic mesothelium in humans. Thus important additional applications of the animal model may be discovered.